Research into novel biologically active compounds is provoking increasing interest, in particular in the field of medicine (M. Hibert, J. Haiech Médecine/Sciences 2000, 16, 1332-1339). Among the multitude of isolated natural products, the heteroaromatic nitrogen-containing compounds occupy an important position, in particular those which are derived from indole. A good number of these indolic compounds possess the “nortryptamine” unit (3′-indolyl methylamine) of formula 1a (1, R═R1═H) or the “tryptamine” unit (2-(3′-indolyl)ethylamine) of formula 2a (2, R═H). In order to find still more original bio-active molecules, the marine medium has become an essential field of research due to the great diversity of its hosts: more than 500,000 species of organisms (D. J. Faulkner Nat. Prod. Rep. 2001, 18, 1-49 and articles reported therein; C.-G. Yang, H. Huang, B. Jiang Cur. Org. Chem. 2004, 8, 1691-1720; W. Gul, M. T. Hamann Life Sciences 2005, 78, 442-453). Their study has made it possible to discover novel indolic alkaloids of original structure characterized by an indolic 1,2-diamine unit of formula 3a (3, R═H), denoted 1-(3′-indolyl)-1,2-diaminoethane.

The strategic importance of effectively accessing these three structures 1a, 2a and 3a and the corresponding derivatives 1, 2 and 3, key units of intermediates in the synthesis of numerous bio-active indolic compounds, has led numerous research groups to develop effective routes for the synthesis of these intermediates. In particular, the introduction of a nitrogen-containing carbon chain directly in position 3 of an indole ring, the most reactive position vis-à-vis the aromatic electrophilic substitution when it is not substituted, has been the subject of a particular study as the judicious choice of the nitrogen-containing electrophilic partner of the indole ring allows direct access to the desired unit.
Thus, the most common reaction for accessing the indolic derivatives 1 possessing the (3′-indolyl)methylamine unit 1a is the Mannich reaction. It involves reacting an aldehyde and an amine with an indole ring in acid medium. Its field of application being limited (A. Heydari, H. Tavakol, S. Aslanzadeh, J. Azarnia, N. Ahmadi Synthesis 2005, 622-626), other processes derived from aminomethylation and aminoalkylation have been developed (H.-J. Grumbach, M. Arend, N. Risch Synthesis 1996, 883-887 and references cited; Y. Gong, K. Kato, H. Kimoto Bull. Chem. Soc. Jpn. 2002, 75, 2637-3645; N. Sakai, M. Hirasawa, M. Hamajima, T. Konakahara J. Org. Chem. 2003, 68, 483-488 and references cited).
The synthesis of indolic derivatives 2 possessing the 2-(3′-indolyl)ethylamine unit 2a from indole requires several stages in order to introduce the two carbon atoms. Other routes, in particular from tryptophan, are also described.
As regards the synthesis of the indolic derivatives possessing the 1-(3′-indolyl)-1,2-diaminoethane unit 3a, to our knowledge, only one process was described before 1997. In 1965, Rajagopalan and Advani described a strategy for synthesis of indolic 1,2-diamines based on the Strecker reaction (P. Rajagopalan, B. G. Advani Tetrahedron Lett. 1965, 2197-2200). It requires several stages from the indole and it leads to protected derivatives of which the protective group of the amines cannot be removed. This process requires prior protection of the indolic nitrogen and does not make it possible to access the unprotected 1,2-diaminated indolic derivatives 3.
Thus, one of the purposes of the present invention involves providing synthesis strategies making it possible to access indolic derivatives possessing the 1-(3′-indolyl)-1,2-diaminoethane unit 3a.
A purpose of the present invention is also to provide antibacterial compounds of novel structures originating from these strategies, having either an intrinsic antibacterial activity or an efflux pump inhibiting activity.